Process for producing 1,2-trans-glycoside compound

ABSTRACT

In preparing a glycoside compound from (a) a furanose compound or pyranose compound, and (b) an alcohol compound, a process for preparing a glycoside compound in which glycosidic bond locates selectively trans form relative to C-2 hydroxyl group, the process comprising using a furanose compound wherein the hydroxyl at the 2-position may have a substituent protected with a group A, or a pyranose compound which may have a substituent 
                         
wherein R 2  and R 3  are the same or different and are each alkyl having 1 to 4 carbon atoms or aryl having or not having a substituent, or R 2  and R 3  are combined to form alkylene having 2 to 4 carbon atoms (the alkylene may be substituted with alkyl having 1 to 4 carbon atoms, or may have intervening phenylene), and m and n are each an integer of 0 or 1.

TECHNICAL FIELD

The present invention relates to a process for selective preparation of1,2-trans glycoside compounds.

BACKGROUND ART

Much attention has been directed in recent years to biological functionsof oligosaccharides as the third biogenic polymers in the living bodyfollowing nucleic acids and proteins. It has been found that theoligosaccharides present on the surfaces of cells have a wide variety offunctions such as intercellular transmission of information andinteraction between the oligosaccharide and an internal matrix such asvirus. It is an urgent problem to clarify the structure-activityrelationship for understanding many of biological processes involvingoligosaccharides. However, naturally occurring oligosaccharide compoundspossess microheterogeneity in structure in terms of branching,stereochemistry, and molecular weight, and chemically pureoligosaccharides are extremely difficult to separate from living bodysamples by purification procedures. In view of such problems, it isstrongly desired to provide by chemical synthesis chemically pureoligosaccharide compounds having a clarified structure.

The 1,2-transglycoside linkage is a typical glycoside linkage which isgenerally found in oligosaccharides. The conventional method ofpreparing this glycoside bond stereoselectively uses 2-acyl protectedglycosides as glycosyl donors, and the acyl group serves asstereodirecting group for the stereoselective formation of 1,2-transglycosides by intramolecular participation. However, this process alwayshas the problem of giving an ortho ester as a by-product.

The present inventor developed an iterative glycosylation reaction forpreparing oligosaccharides by repeating the same reaction with use ofthioglycoside only (Nonpatent Literature 1). This method was veryeffective for saccharide derivatives having an amino group at the2-position, such as glucosamine, whereas it was not effective for otherselective formation of ortho ester in the case where a saccharidederivative having a hydroxyl group at the 2-position, such as glucose,galactose or the like, was used.

wherein Ph is phenyl, and Bn is benzyl.[Nonpatent Literature 1] Angew Chem. Int. Ed. 2004, 43, 2145.

An object of the present invention is to provide a process forselectively preparing a 1,2-transglycoside compound by inhibiting theformation of an o-ester by-product in saccharide derivatives having ahydroxyl group at the 2-position.

DISCLOSURE OF THE INVENTION

The present invention provides the process to be described below forpreparing a 1,2-transglycoside compound, and2-phosphonoyl-1,2-transglycoside compounds for use in the preparationprocess.

1. In preparing a glycoside compound from (a) a furanose compound orpyranose compound, and (b) an alcohol compound, a process for preparinga glycoside compound in which glycosidic bond locates selectively transform relative to C-2 hydroxyl group, the process comprising using afuranose compound wherein the hydroxyl at the 2-position may have asubstituent protected with a group A, or a pyranose compound which mayhave a substituent

wherein R² and R³ are the same or different and are each alkyl having 1to 4 carbon atoms or aryl having or not having a substituent, or R² andR³ are combined to form alkylene having 2 to 4 carbon atoms (thealkylene may be substituted with alkyl having 1 to 4 carbon atoms, ormay have intervening phenylene), and m and n are each an integer of 0 or1.

2. A process for preparing a glycoside compound having a trans formaccording to claim 1 wherein the furanose compound is arabofuranose,erythrofuranose, glucofuranose, ribofuranose, threofuranose orxylofuranose, the pyranose compound is arabopyranose, altropyranose,glucopyranose, galactopyranose, glopyranose, mannopyranose,ribopyranose, xylopyranose or glucopyranuronic acid, and the alcoholcompound is an aliphatic alcohol having 1 to 4 carbon atoms, alicyclicalcohol having 5 to 8 carbon atoms, aromatic alcohol, furanose,pyranose, aminopyranose, anhydrosugar, polysaccharide, N-acetylpyranoseor glycerol.

3. A process for preparing a 2-phosphonoyl-1,2-transglycoside compoundof the formula (3) comprising reacting an alcohol compound of theformula (2) with a 2-phosphonoylpyranose compound of the formula (1)Q¹-Z  (1)Q¹=

wherein Z is a group —S—R¹, group —SO—R¹, group —Se—R¹, group—O—C(═NH)CX₃, halogen atom, alkoxyl, alkenyloxy, group —P(OR¹)₃ or group—PO(OR¹)₃, R¹ being alkyl having 1 to 20 carbon atoms, aryl having ornot having a substituent or heteroaromatic group, X being a halogenatom, R⁴, R⁵ and R⁶ may be the same or different and are each aprotective group for the saccharide hydroxyl group, E is methylene orcarbonyl, and A is as defined aboveQ²-OH  (2)wherein Q² is alkyl having 1 to 4 carbon atoms, cycloalkyl having 5 to 8carbon atoms and having or not having a substituent at an optionalposition or one of the following groups

wherein L¹ is a group —OA¹, —OG or —N(J¹) (J²), A¹ being a group shownbelow, G being a protective group for the saccharide hydroxyl, and J¹and J² being each a hydrogen atom or a protective group for amino

R^(2′) and R^(3′) are the same or different and are each alkyl having 1to 4 carbon atoms or aryl having or not having a substituent, or R^(2′)and R^(3′) are combined with each other to form alkylene having 2 to 4carbon atoms (the alkylene may be substituted with alkyl having 1 to 4carbon atoms or may have an intervening phenylene), m′ and n′ are eachan integer of 0 or 1. Z¹ is a group —S—R¹, group —SO—R^(1′), group—Se—R^(1′), group —O—C(═NH)CX′₃, halogen atom, alkoxyl, alkenyloxy,group —P(OR^(1′))₃, group —PO(OR^(1′))₃ or —OG¹, R^(1′) being alkylhaving 1 to 20 carbon atoms, aryl having or not having a substituent orheteroaromatic group, X′ being a halogen atom, G¹ being a protectivegroup for the saccharide hydroxyl, R⁷, R⁸ and R⁹ may be the same ordifferent and are each a protective group for the saccharide hydroxylgroup, E¹ is methylene or carbonylQ^(1a)-O-Q²  (3)Q^(1a)=

wherein Q², A, R⁴, R⁵ and R⁶ are as defined above.

4. A process for preparing a 2-phosphonoyl-1,2-transglycoside compoundof the formula (3a) comprising reacting an alcohol compound of theformula (2a) with a 2-phosphonoylpyranose compound of the formula (1)Q^(2a)-OH  (2a)wherein Q^(2a) is one of the groups given below, A¹, R⁷, R⁸, R⁹ and E¹are as defined above, Z² is a group —S—R^(1′), group —SO—R^(1′), group—Se—R^(1′), group —O—C(═NH)CX′₃, halogen atom, alkoxyl, alkenyloxy,group —P(OR^(1′))₃ or group —PO(OR^(1′))₃, and R^(1′) and X′ are asdefined above

Q^(1a)-O-Q^(2a)  (3a)wherein Q^(1a) and Q^(2a) are as defined above.

5. A process for preparing a 2-phosphonoyl-1,2-transglycoside compoundcomprising repeating the step of reacting an alcohol compound with a2-phosphonoyl-1,2-transglycoside compound of the formula (3a) at leastonce.

6. A process for preparing a 1,2-transglycoside compound of the formula(4) comprising reacting a base with a 2-phosphonoyl-1,2-transglycosidecompound of the formula (3)Q³-O-Q⁴  (4)Q³=

wherein R⁴, R⁵, R⁶ and E are as defined above, and Q⁴ is alkyl having 1to 4 carbon atoms, cycloalkyl having 5 to 8 carbon atoms and having ornot having a substituent at an optional position or one of the groupsgiven below

wherein L² is the group —OH, —OG or —N(J¹) (J²), and Z¹, R⁷, R⁸, R⁹, E¹,G, J¹ and J² are as defined above.

7. A phosphonoylpyranose compound of the formula (1).

8. A 2-phosphonoyl-1,2-transglycoside compound of the formula (3).

9. A 2-phosphonoyl-1,2-transglycoside compound of the formula (3a).

According to the present invention, a glycoside compound having a1,2-trans stereochemistry can be prepared selectively by using a2-phosophonoylfuranose compound or 2-phosophonoylpyranose compoundcomprising a furanose compound or pyranose compound wherein the hydroxylgroup at the 2-position is protected with a specific phosphoric acidester.

The substituents given below are herein described.

Examples of alkyl groups having 1 to 4 carbon atoms are methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl. tert-butyl, etc.

Examples of aryl groups can be phenyl, naphthyl, etc. These groups mayhave a substituent at an optional position. Examples of substituents area hydrogen atom, alkyl having 1 to 4 carbon atoms, etc. Examples ofhalogen atoms are fluorine atom, chlorine atom, bromine atom and iodineatom. The same or different substituents may be present, and one to anumber of substituents that can serve as such can be present.

Examples of alkylene groups having 2 to 4 carbon atoms are dimethylene,trimethylene and tetramethylene. These groups may be substituted withalkyl having 1 to 4 carbon atoms at an optional position, or may haveintervening phenylene. More specific examples are the group —(CH₂)₂—,group —(CH₂)₃—, group —(CH₂)₄—, group —C(CH₂)₂C(CH₂)₂—, group—CH₂CH(CH₂)CH₂—, group —CH(CH₂)CH₂CH(CH₂)—, group —C(CH₂)₂CH₂CH₂—, group—CH₂C(CH₂)₂CH₂—, —CH₂CH₂—C₆H₄—CH₂—, etc.

Examples of alkoxyl groups are those having 1 to 4 carbon atoms, such asmethoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxyand tert-butoxy.

Examples of alkenyloxy groups are those having 2 to 4 carbon atoms suchas vinyloxy, propenyloxy and butenyloxy.

Examples of groups for protecting the saccharide hydroxyl group are notlimited particularly insofar as they are useful for protecting thehydroxyl group of saccharide compounds.

Examples of such groups are benzyl, methoxymethyl,tert-butyldimethylsilyl, triisopropylsilyl, benzoyl, acetyl, pivaloyl,levulyl, etc. Two adjacent hydroxyl groups may provide a ring withmethylene, ethylene, isopropylidene or benzylidene.

Examples of cycloalkyl groups having 5 to 8 carbon atoms arecyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. These groups mayhave a substituent at an optional position. Examples of substituents arealkyl groups having 1 to 4 carbon atoms. More specific examples are4,5-dimethylpentyl, 4-methylhexyl, 3,5-dimethylhexyl, 4-tert-butylhexyl,2,4,6-trimethylhexyl, etc.

According to the present invention, 1,2-transglucoside compounds areprepared using a furanose compound or pyranose compound wherein thehydroxyl group at the 2-position is protected with a group A and whichmay have a substituent, and an alcohol compound

wherein R², R³, m and n are as defined above.

The furanose compound to be used is not particularly limited insofar asit has a hydroxyl group at the 2-position. For example, the furanosecompound is arabofuranose, erythrofuranose, glucofuranose, ribofuranose,threofuranose or xylofuranose. These furanose compounds may have asubstituent. Examples of substituents are protective groups forsaccharide hydroxyl groups, and groups which comprise a monosaccharideor polysaccharide and which may have a hydroxyl group as protected witha protective group.

The pyranose compound to be used is not limited specifically insofar asit has a hydroxyl group at the 2-position. For example, the pyranosecompound is arabopyranose, altropyranose, glucopyranose,galactopyranose, glopyranose, mannopyranose, ribopyranose, xylopyranoseor glucopyranuronic acid, These pyranose compounds may have asubstituent. Examples of substituents are protective groups forsaccharide hydroxyl groups, and groups which comprise a monosaccharideor polysaccharide and which may have a hydroxyl group as protected witha protective group.

Examples of groups A are given below.

Among these, especially preferable to use are the groups (A-3) and(A-5).

For a simplified description, the present invention as practiced byusing pyranose compounds only will be described below, whereas theinvention can be practiced similarly with use of furanose compounds.

The pyranose compound wherein the hydroxyl group at the 2-position isprotected with a group A can be prepared by reacting a phosphoric acidhalide of the formula (5) with a pyranose compoundA-X³  (5)wherein A is as defined above, and X³ is a halogen atom.

For example, the 2-phosphonoyl-1,2-transpyranose compound of the formula(1) can be prepared according to Reaction Formula-1 given below.

wherein A, R⁴, R⁵, R⁶, Z and X³ are as defined above.

According to Reaction Formula-1, the 2-phosphonoyl-1,2-transpyranosecompound of the formula (1-Q¹-1), (1-Q²-1) or (1-Q³-1) corresponding tothe compound of the formula (1) can be prepared by reacting thephosphoric acid halide of the formula (5) with a pyranose compound ofthe formula (6-1), (6-2) or (6-3).

This reaction is conducted usually in a solvent by causing a base to acton the pyranose compound of the formula (6-1), (6-2) or (6-3) andthereafter causing the phosphoric acid halide of the formula (5) to acton the resulting product. The solvent to be used is not limitedspecifically insofar as it is inert to the reaction. Examples of usefulsolvents are hexane, heptane, pentane and like aliphatic hydrocarbons,cyclohexane and like aliphatic hydrocarbons, benzene, toluene, xyleneand like aromatic hydrocarbons, dichloromethane, chloroform,1,2-dichloroethane, 1,1,1-trichloroethane, tetrachloroethylene,trichloroethylene, carbon tetrachloride, chlorobenzene, dichlorobenzeneand like hydrocarbon halides, diethyl ether, isopropyl ether,tetrahydrofuran, dioxane, monoglyme and like ethers,N,N-dimethylformamide, N,N-dimethylacetamide,1,3-dimethylimidazolidinone and like amides, dimethyl sulfoxide and likesulfoxides, or solvent mixtures of such solvents. Especially preferableamong these are ethers, amides and sulfoxides.

These solvents are used in an amount of about 1 to about 100 liters,preferably about 5 to about 20 liters, per kg of the pyranose compoundof the formula (6-1), (6-2) or (6-3).

Examples of useful bases are sodium carbonate, potassium carbonate andlike alkali metal carbonates, sodium hydride and like alkali metalhydrides, triethylamine, pyridine, DBU and like organic bases, and butyllithium, lithium diisopropylamide, lithium bistrimethylsilylamide andlike lithium salts.

These bases can be used singly, or at least two of them are usable incombination. These bases are used in an amount of 1 to 10 equivalents,preferably 1 to 5 equivalents, based on the pyranose compound of theformula (6-1), (6-2) or (6-3).

Although the pyranose compound of the formula (6-1), (6-2) or (6-3) andthe phosphoric acid halide of the formula (5) can be used in a desiredratio, it is desirable to use 1.0 to 2.0 moles of the latter per mole ofthe former.

The reaction temperature, which can be set to a desired value in therange of −20 to 100° C., is usually preferably 0 to 30° C. The reactiontime is not limited particularly and is usually about 30 minutes toabout 3 hours.

The 2-phosphonoylpyranose compound which is obtained by the aboveprocedure and wherein the hydroxyl group at the 2-position is protectedwith a phosphoric acid ester is a novel compound which has not beendisclosed in literature.

The pyranose compounds of the formulae (6-1), (6-2) and (6-3) can beprepared, for example, by the known conventional processes to bedescribed below.

The compound of the formula (6-1) glucose

REFERENCE LITERATURE

-   Carbohydr. Res. 1992, 236, 73.-   Can. J. Chem. 1965, 43, 2199.-   Org. Lett. 2004, 3797.    The compound of the formula (6-2) galactose

TL: Tetrahedron Lett. 1989, 30, 2537.NAP: 2-naphthylmethylThe compound of the formula (6-3) mannose

The alcohol compound to be used is not limited particularly insofar asthe compound forms a glycoside linkage with the 1-position of thepyranose. Examples of useful alcohol compounds are aliphatic alcoholshaving 1 to 4 straight-chain or branched-chain carbon atoms, such asmethanol, ethanol, propanol, isopropanol and butanol, alicyclic alcoholshaving 5 to 8 carbon atoms, such as cyclohexanol, cyclopentanol andcyclooctanol, aromatic alcohols such as phenol, cresol and naphthol,furanoses such as arabofuranose, erythrofuranose, glucofuranose,galactofuranose, fructofuranose, ribofuranose, deoxyribofuranose,threofuranose and xylofuranose, pyranoses such as arabopyranose,altropyranose, glucopyranose, galactopyranose, glopyranose,mannopyranose, ribopyranose, xylopyranose and glucopyranuronic acid,aminopyranoses such as 2-amino-2-deoxygalactopyranose and2-amino-2-deoxyglucopyranose, anhydrosugars such as glucosamine,polysaccharides such as gentiobiose, sucrose, cellobiose, lactose,allolactose, maltose, trehalose, N-acetyllactosamine, kanamycin andkasugamycin, N-acetylpyranoses such as2-acetamido-2-deoxygalactopyranose, 2-acetamido-2-deoxyglucopyranose,2-acetamido-2-deoxymannopyranose and aspartylglycosylamine, glycerols,etc. These compounds may have a substituent that will not adverselyaffect the reaction.

The glycoside compound of trans form can be obtained by causing analcohol compound to act on the pyranose compound wherein the hydroxylgroup at the 2-position is protected with the group A. This reaction canbe conducted by a known conventional process comprising activating thecarbon at the 1-position of the pyranose compound and causing thealcohol to act on the compound. The reaction can be represented, forexample, by Reaction Formula-2 given below.

wherein Q¹, Q^(1a) and Q² are as defined above, Z is a group —S—R¹,group —SO—R¹, group —Se—R¹, group —O—C(═NH)CX₃, halogen atom, alkoxyl,alkenyloxy, group —P(OR¹)₃ or group —PO(OR¹)₃, R¹ being alkyl having 1to 20 carbon atoms, aryl having or not having a substituent orheteroaromatic group, X being a halogen atom.

Examples of alkyl groups having 1 to 20 carbon atoms are methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, hexyl,octyl, decyl, dodecyl, hexadecyl, octadecyl, eicosyl, etc. Aryl groupswhich may have a substituent are the same as those already mentioned.The heteroaromatic group is, for example, pyridyl.

The 2-phosphonoyl-1,2-transglycoside compound of the formula (3) can beprepared by activating a 2-phosphonoylpyranose compound of the formula(1) as the pyranose compound wherein the hydroxyl group at the2-position is protected, and thereafter causing an alcohol compound ofthe formula (2) to act on the activated compound.

In the case where Z is a group —S—R¹ or group —SO—R¹ in the2-phosphonoylpyranose compound of the formula (1), the alcohol compoundof the formula (2) can be reacted with the compound (1), for example,according to J. Am. Chem. Soc., 2001, 123, 9015 or “Carbohydrates inChemistry and Biology,” Wiley-VCH, 2000, Vol. 1, Chap. 4 (pp. 93-134),after the compound (1) has been activated.

This reaction is conducted in a solvent. Examples of useful solvents aredichloromethane, dichloroethane, tetrachloroethane and like hydrocarbonhalides, toluene and like aromatic hydrocarbons, etc., among whichdichloromethane and tetrachloroethane are desirable. The solvent shouldbe made anhydrous to such an extent as to avoid the influence on thereaction. The solvent is used in an amount of 1 to 100 liters,preferably about 5 to about 50 liters, per kg of the compound (1).

The compound (1) is activated by causing 2,6-tert-butyl-4-methylpyridine(DTBMP), benzenesulfinylpyridine (BSP), trifluoromethanesulfonicanhydride (Tf₂O) or the like to act thereon.

DTBMP is used in an mount of about 1 to about 5 mole equivalents, BSP inan amount of about 1 to 2 equivalents, or Tf₂O in an amount of about 1to about 2 equivalents, per mol of the compound (1).

The reaction is conducted preferably in an anhydrous system, preferablyin the presence of a dehydrating agent such as a molecular sieve(molecular sieve 4A).

Since the activated compound obtained by the intermediate step is low inthermal stability, it is desired to conduct the reaction at a lowtemperature of up to −40° C.

The alcohol compound (2) is added to the compound (1) as activated inthis way, whereby the 2-phosphonoyl-1,2-glycoside compound (3) can beprepared.

The alcohol compound (2) is used in an amount of 0.8 to 3 moleequivalents, preferably 1.0 to 2.0 mole equivalents, per mole of thecompound (1).

The reaction temperature can be set to a desired value in the range of−80 to −40° C., and is usually preferably −70 to −45° C. Although notlimited particularly, the reaction time is usually about 1 minute toabout 1 hour.

The 2-phosphonoylpyranose compound of the formula (1) can be activated,for example, according to the method described in the followingliterature.

(a) In case where Z is a group —O—C(═NH)CX¹ ₃ “Preparative CarbohydrateChemistry”, Marcel Dekker, Inc., 1997, Chap 12 (pp 283-312) and“Carbohydrates in Chemistry and Biology”, Wiley-VCH, 2000, Vol. 1, Chap2 (pp 5-59)

(b) In case where Z is chlorine atom or bromine atom Angew. Chem. Int.Ed. 1982, 21, 155-224

(c) In case where Z is fluoride atom; “Preparative CarbohydrateChemistry”, Marcel Dekker, Inc., 1997, Chap 13 (pp 313-338)

(d) In case where Z is alkenyloxy group: “Preparative CarbohydrateChemistry”, Marcel Dekker, Inc., 1997, Chap 14 (pp 339-356) and“Carbohydrates in Chemistry and Biology”, Wiley-VCH, 2000, Vol. 1, Chap6 (pp 135-154)

(e) In case where Z is a group —P(OR¹)₃; “Carbohydrates in Chemistry andBiology”, Wiley-VCH, 2000, Vol. 1, Chap 5 (pp 117-134)

(f) In case where Z is a group —PO(OR¹)₃; J. Chem. Soc., Chem. Commun.1989, 685 and J. Am. Chem. Soc. 2001, 123, 9545

The process of the invention is capable of inhibiting the formation ofthe o-ester by-product resulting from the conventional glycosilationreaction of pyranose compounds of 1,2-trans form, affording1,2-transglycoside compounds with high selectivity.

FIG. 1 schematically shows the advantage of the preparation process ofthe invention

FIG. 1

wherein A, Q² and Z are as defined above.

With reference to FIG. 1 showing the present invention, an alcoholcompound of the formula (2) is caused to act on a 2-phosphonoylpyranosecompound (1 or III) in which the hydroxyl group at the 2-position isprotected with a specified phosphoric acid ester serving as a protectivegroup A to produce an o-glycoside compound (II or IV) wherein thestereoarrangement of the o-glycoside linkage at the 1-position of thepyranose ring and the protected hydroxyl group at the 2-position is madeto have a trans form with high selectivity. Furthermore the processensures the selectivity of the stereoarrangement without beinginfluenced greatly by the kind of the alcohol compound used.

A glycoside linkage can be formed anew by causing an alcohol compound toact on 2-phosphonoyl-1,2-transglycoside compound of the formula (3a)which is included among the 2-phosphonoylk-1,2-transglycoside compoundsof the formula (3) prepared by the present process. When the alcoholcompound to be used is an alcohol compound of the formula (2a), itbecomes possible to form another glycoside linkage, with the result thatthe oligosaccharide can be lengthened as desired in accordance with thenumber of repetitionsQ^(1a)-O-Q^(2a)  (3a)wherein Q^(1a) and Q^(2a) are as defined aboveQ^(2a)-OH  (2a)wherein Q^(2a) is as defined above.

The 2-phosphonoyl-1,2-transglycoside compound of the formula (3) and the2-phosphonoyl-1,2-transglycoside compound of the formula (3a) thusobtained are novel compounds which have not been disclosed inliterature.

The protective group A for the 2-position hydroxyl group is removableeasily from the glycoside compounds obtained.

For example, as represented by Reaction Formula-3, a base is caused toact on the 2-phosphonoyl-1,2-transglucoside compound of the formula (3),whereby the group A is removed to give a 1,2-transglycoside compound ofthe formula (4).

wherein Q^(1a), Q², Q³ and Q⁴ are as defined above.

The base to be used is, for example, sodium methoxide, sodium ethoxide,potassium tert-butoxide or like alkali metal alkoxide, or sodiumhydroxide, potassium hydroxide or like alkali metal hydroxide.

These bases can be used singly, or at least two of them are usable incombination. The base is used in an amount of 1 to 10 equivalents,preferably 2.0 to 5.0 equivalents, based on the compound (3).

The reaction is conducted in a solvent. The solvent to be used ismethanol, ethanol, isopropanol or like alcohol, water, or a solventmixture of such solvents, or a solvent mixture of water or alcohol andtetrahydrofuran or dioxane.

These solvents are used in an amount of about 1 to about 100 liters,preferably about 5 to about 20 liters, per kg of the compound (3).

The reaction temperature can be set to a desired value in the range of0° C. to the boiling point of the solvent, and is usually preferablyroom temperature to about 60° C. Although not limited particularly, thereaction time is usually about 0.5 to about 10 hours to achieve asatisfactory result

BEST MODE OF CARRYING OUT THE INVENTION

The present invention will be described below in greater detail withreference to examples. However, the invention is not limited to theseexamples. The parts are by weight unless otherwise specified. Withreference to the table, SPh stands for thiophenyl Bn for benzyl, TBS fortert-butyldimethylsilyl, c-Hex for cyclohexyl, Ph for phenyl and TCPNfor tetrachlorophthaloyl.

REFERENCE EXAMPLE 1 Preparation of Phosphoric Acid Halide A-X³ (A=A−2,X³=Cl)

A dichloromethane solution (40.0 ml) of 2,3-dimethyl-2,3-butanediol (2.4g, 20.0 mmols) was added to a solution of phosphorus oxychloride (3.7 g,24.0 mmols) and triethylamine (4.9 g, 48.0 mmols) at room temperature,and the mixture was stirred at the same temperature for 2 hours. Theresulting reaction mixture was concentrated in a vacuum, giving a crudeproduct, which was purified by sublimation to give the desired productin the form of a white solid in a yield of 80%.

¹H-NMR (400 MHz, CDCl₃) 1.51 (s, 6H), 1.53 (s, 6H).

EXAMPLE 1 Phenyl 3,4,6-tri-O-benzyl-2-O-(1,1,2,2-tetramethyl-dimethylenephosphonoyl)-β-D-thioglucopyranoside

To 60-72% solution of sodium hydride (80.0 mg, 2.0 mmols) was added atroom temperature a solution of 3,4,6-tri-O-benzyl-β-D-thioglucopyranosid(542.7 mg, 1.0 mmol) in 2.0 ml of THF. Thirty minutes later,2,3-dimethyl-2,3-butylene phosphorochloridate (297.9 mg, 1.5 mmols) wasadded to the reaction mixture. The reaction was terminated withsaturated aqueous solution of sodium bicarbonate 3.5 hours later. Theorganic layer was separated off, the aqueous layer was subjected toextraction with ethyl acetate, and the extraction organic layers wereall combined together and washed with saturated saline solution. Thewashed layer was dried over magnesium sulfate and thereafter treated byfiltration. The organic solvent was removed from the filtrate in avacuum by a rotary evaporator to obtain a crude product.

The desired product (456.5 mg) was obtained from the crude product byflash chromatography (silica gel 37 g; elution with 40% ethyl acetate inhexane).

Yield: 65%

Properties: amorphous powder

¹H NMR (400 MHz, CDCl₃): 1.35 (s, 3H), 1.39 (s, 3H), 1.42 (s, 3H), 1.49(s, 3H), 3.50-3.57 (m, 1H), 3.61 (t, J=9.2 Hz, 1H), 3.65-3.73 (m, 2H),3.77 (dd, J=11.0, 1.4 Hz, 1H), 4.42-4.52 (m, 1H), 4.51 (d, J=12.0 Hz,1H), 4.53 (d, J=12.8 Hz, 1H), 4.56 (d, J=12.0 Hz, 1H), 4.66 (d, J=10.0Hz, 1H), 4.76 (d, J=10.8 Hz, 2H), 4.96 (d, J=10.8 Hz, 1H), 7.14-7.20 (m,2H), 7.22-7.35 (m, 14H), 7.38-7.43 (m, 2H), 7.60-7.66 (m, 2H).

¹³C NMR (100 MHz, CDCl₃): 23.67 (CH₃, J_(CP)=4.6 Hz), 23.72 (CH₃,J_(CP)=5.4 Hz), 24.02 (CH₃, J_(CP)=5.3 Hz), 24.15 (CH₃, J_(CP)=5.4 Hz),68.89 (CH₂), 73.42 (CH₂), 74.92 (CH₂), 75.39 (CH₂), 77.55 (CH), 77.95(CH, J_(CP)=6.9 Hz) 79.37 (CH), 84.94 (CH, J_(CP)=3.1 Hz), 86.82 (CH,J_(CP)=3.8 Hz), 88.20 (C), 88.38 (C), 127.51 (CH), 127.54 (CH), 127.62(CH, 2C), 127.75 (CH, 2C), 127.84 (CH, 2C), 128.11 (CH, 2C), 128.17 (CH,2C), 128.30 (CH, 2C), 128.36 (CH, 2C), 128.74 (CH, 2C), 132.86 (CH, 2C),133.09 (C), 137.92 (C), 138.07 (C), 138.18 (C).

In the same manner, Examples 2 to 10 were conducted.

EXAMPLE 2 Phenyl 3,4,6-tri-O-benzyl-2-O-(diphenoxyphosphonoyl)-β-D-thioglucopyranoside

Yield: 57%

Properties: white powder

¹H-NMR (400 MHz, CDCl₃): 3.53-3.60 (m, 1H), 3.66-3.85 (m, 4H), 4.52 (d,J=12.0 Hz, 1H), 4.55 (d, J=11.6 Hz, 1H), 4.58 (d, J=12.0 Hz, 1H),4.54-4.66 (m, 1H), 4.73 (d, J=8.8 Hz, 1H), 4.73 (d, J=9.6 Hz, 1H), 4.83(d, J=10.4 Hz, 1H), 4.90 (d, J=10.4 Hz, 1H), 7.00-7.53 (m, 30H).

EXAMPLE 3 Phenyl 3,4,6-tri-O-benzyl-2-O-(trimethylenephosphonoyl)-β-D-thioglucopyranoside

Yield: 52%

Properties: amorphous powder

¹H NMR (400 MHz, CDCl₃): 1.73-1.87 (m, 1H), 1.96-2.11 (m, 1H), 3.57-3.63(m, 1H), 3.66 (dd, J=9.8, 8.6 Hz, 1H), 3.72 (dd, J=11.0, 4.6 Hz, 1H),3.76-3.83 (m, 1H), 3.86 (t, J=8.6 Hz, 1H), 4.32-4.23 (m, 5H), 4.54 (d,J=12.4 Hz, 1H), 4.57 (d, J=11.2 Hz, 1H), 4.59 (d, J=10.8 Hz, 1H), 4.78(d, J=11.2 Hz, 1H), 4.79 (d, J=10.0 Hz, 1H), 4.82 (d, J=10.4 Hz, 1H),4.96 (d, J=10.4 Hz, 1H), 7.17-7.22 (m, 2H), 7.22-7.39 (m, 14H),7.40-7.45 (m, 2H), 7.61-7.67 (m, 2H).

¹³C NMR (100 MHz, CDCl₃): 25.86 (CH₂, J_(CP)=6.9 Hz), 68.41 (CH₂,J_(CP)=8.4 Hz), 68.48 (CH₂, J_(CP)=6.8 Hz), 68.82 (CH₂), 73.39 (CH₂),74.87 (CH₂), 75.34 (CH₂), 77.65 (CH, J_(CP)=3.8 Hz), 77.66 (CH), 79.31(CH), 84.63 (CH, J_(CP)=1.5 Hz), 85.94 (CH, J_(CP)=4.6 Hz), 127.53 (CH),127.58 (CH, 2C), 127.60 (CH), 127.78 (CH), 127.83 (CH, 2C), 127.94 (CH),128.07 (CH, 2C), 128.27 (CH, 2C), 128.31 (CH, 2C), 128.38 (CH, 2C),128.85 (CH, 2C), 132.19 (C), 132.91 (CH, 2C), 137.83 (C), 137.97 (C),138.15 (C).

HRMS (FAB) m/z: Calcd for C₃₆H₄₀O₈PS(M+H)⁺, 663.2182; Found 663.2194.

EXAMPLE 4 Phenyl 3,4,6-tri-O-benzyl-2-O-(2-methyltrimethylenephosphonoyl)-β-D-thioglucopyranoside

Yield: 55% (diastereo ratio 79:21)

Properties: white powder

HRMS (FAB) m/z: Calcd for C₃₇H₄₂O₈PS (M+H)⁺, 677.2338; Found 677.2346.

EXAMPLE 5 Phenyl3,4,6-tri-O-benzyl-2-O-[(1R,3R)-1,3-dimethyltrimethylenephosphonoyl]-β-D-thioglucopyranoside

Yield: 51%

Properties: amorphous powder

¹H NMR (400 MHz, CDCl₃): 1.31 (dd, J=6.4, 1.6 Hz, 3H), 1.45 (dd, J=6.6,1.0 Hz, 1H), 1.80-1.88 (m, 1H), 1.93-2.02 (m, 1H), 3.52-3.60 (m, 1H),3.61 (t, J=9.2 Hz, 1H), 3.68 (dd, J=11.0, 4.6 Hz, 1H), 3.76 (dd, J=10.8,1.6 Hz, 1H), 3.84 (t, J=8.6 Hz, 1H), 4.38-4.50 (m, 1H), 4.51 (d, J=12.0Hz, 1H), 4.53 (d, J=11.2 Hz, 1H), 4.57 (d, J=11.6 Hz, 1H), 4.67-4.77 (m,1H), 4.74 (d, J=10.4 Hz, 2H), 4.79 (d, J=10.4 Hz, 1H), 4.78-4.90 (m,1H), 4.94 (d, J=10.8 Hz, 1H), 7.14-7.18 (m, 2H), 7.22-7.34 (m, 16H),7.38-7.43 (m, 2H), 7.59-7.64 (m, 2H).

¹³C NMR (100 MHz, CDCl₃): 21.26 (CH₃, J_(CP)=3.8 Hz), 21.72 (CH₃,J_(CP)=6.9 Hz), 37.71 (CH₂, J_(CP)=6.1 Hz), 68.89 (CH₂), 72.83 (CH,J_(CP)=6.9 Hz), 73.39 (CH₂), 74.01 (CH, J_(CP)=6.1 Hz), 74.90 (CH₂),75.24 (CH₂), 77.62 (CH) 78.02 (CH, J_(CP)=6.9 Hz), 79.24 (CH), 84.79(CH, J_(CP)=2.3 Hz), 86.36 (CH, J_(CP)=3.8 Hz), 127.52 (CH, 2C), 127.60(CH, 2C), 127.76 (CH, 2C), 127.86 (CH, 4C), 128.20 (CH, 2C), 128.30 (CH,2C), 128.36 (CH, 2C), 128.80 (CH, 2C), 132.72 (CH, 2C), 132.82 (C),137.88 (C), 138.13 (C), 138.19 (C).

HRMS (FAB) m/z: Calcd for C₃₈H₄₄O₈PS (M+H)⁺, 691.2495; Found 691.2491.

EXAMPLE 6 Phenyl3,4,6-tri-O-benzyl-2-O-[(1S,3S)-1,3-dimethyltrimethylenephosphonoyl]-β-D-thioglucopyranoside

Yield: 48%

Properties: amorphous powder

¹H NMR (400 MHz, CDCl₃): 1.37 (dd, J=6.4, 0.8 Hz, 3H), 1.45 (dd, J=6.4,2.0 Hz, 3H), 1.80-1.88 (m, 1H), 1.96-2.03 (m, 1H), 3.52-3.64 (m, 2H),3.67 (dd, J=11.0, 4.6 Hz, 1H), 3.73 (t, J=8.4 Hz, 1H), 3.76 (dd, J=11.0,1.8 Hz, 1H), 4.43 (ddd, J=11.4, 9.4, 9.0 Hz, 1H), 4.51 (d, J=12.0 Hz,1H), 4.52 (d, J=10.8 Hz, 1H), 4.56 (d, J=12.0 Hz, 1H), 4.69 (d, J=9.6Hz, 1H), 4.75 (d, J=10.8 Hz, 2H), 4.71-4.84 (m, 2H), 4.99 (d, i=10.8 Hz,1H), 7.13-7.18 (m, 2H), 7.21-7.36 (m, 14H), 7.39-7.44 (m, 2H), 7.58-7.64(m, 2H).

¹³C NMR (100 MHz, CDCl₃): 21.30 (CH₃, J_(CP)=5.4 Hz), 21.86 (CH₃,J_(CP)=7.6 Hz), 37.79 (CH₂, J_(CP)=6.9 Hz), 68.93 (CH₂), 72.54 (CH,J_(CP)=6.1 Hz), 73.39 (CH₂), 74.04 (CH, J_(CP)=6.9 Hz) 74.93 (CH₂),75.46 (CH₂), 77.44 (CH), 77.56 (CH, J_(CP)=6.8 Hz), 79.36 (CH), 85.11(CH, J_(CP)=2.3 Hz), 86.11 (CH, J_(CP)=4.6 Hz), 127.52 (CH), 127.54(CH), 127.58 (CH, 2C), 127.76 (CH), 127.83 (CH), 127.88 (CH, 2C), 128.12(CH, 2C), 128.22 (CH, 2C), 128.30 (CH, 2C), 128.36 (CH, 2C), 128.83 (CH,2C), 132.47 (C), 132.79 (CH, 2C), 137.89 (C), 138.08 (C), 138.18 (C).

HRMS (FAB) m/z: Calcd for C₃₈H₄₄O₈PS (M+H)⁺, 691.2495; Found 691.2515.

EXAMPLE 7 Phenyl 3,4,6-tri-O-benzyl-2-O-(1,1-dimethyltrimethylenephosphonoyl)-β-D-thioglucopyranoside

Yield: 54% (diastereo ratio 69:31)

Properties: amorphous powder

HRMS (FAB) m/z: Calcd for C₃₈H₄₄O₈PS (M+H)⁺, 691.2495;

Found 691.2483.

EXAMPLE 8 Phenyl3,4,6-tri-O-benzyl-2-O-(1,1,3,3-tetramethyl-trimethylenephosphonoyl)-β-D-thio-glucopyranoside

Yield: 91%

Properties: amorphous powder

¹H NMR (400 MHz, CDCl₃): 1.36 (s, 3H), 1.48 (s, 3H), 1.49 (s, 3H), 1.57(s, 3H), 1.97 (dd, J=14.8, 0.8 Hz, 1H), 2.04 (dd, J=14.8, 1.2 Hz, 1H),3.55 (ddd, J=9.7, 4.9, 1.7 Hz, 1H), 3.61 (t, J=9.2 Hz, 1H), 3.64-3.76(m, 3H), 4.45-4.50 (m, 1H), 4.52 (d, J=10.4 Hz, 1H), 4.52 (d, J=10.8 Hz,1H), 4.57 (d, J=12.0 Hz, 1H), 4.68 (d, J=10.0 Hz, 1H), 4.74 (d, J=11.2Hz, 1H), 4.77 (d, J=10.0 Hz, 1H), 5.01 (d, J=10.4 Hz, 1H), 7.15-7.17 (m,2H), 7.23-7.33 (m, 14H), 7.42-7.44 (m, 2H), 7.61-7.63 (m, 2H).

¹³C NMR (100 MHz, CDCl₃): 30.53 (d, J_(CP)=3.8 Hz, CH₃), 30.56 (d,J_(CP)=3.8 Hz, CH₃), 30.69 (d, J_(CP)=5.3 Hz, CH₃), 31.10 (d, J_(CP)=5.4Hz, CH₃), 47.30 (d, J_(CP)=6.8 Hz, CH₂), 68.97 (CH₂), 73.38 (CH₂), 74.86(CH₂), 75.11 (CH₂), 77.56 (CH), 77.73 (d, J_(CP)=6.8 Hz, CH), 79.25(CH), 82.13 (d, J_(CP)=6.1 Hz, C), 82.19 (d, J_(CP)=6.1 Hz, C), 85.11(d, J_(CP)=2.3 Hz, CH), 86.70 (d, J_(CP)=54.6 Hz, CH), 127.36 (CH),127.48 (CH), 127.60 (CH, 3C), 127.72 (CH, 2C), 127.79 (CH, 2C), 127.88(CH, 2C), 128.10 (CH, 2C), 128.28 (CH, 2C), 128.33 (CH, 2C), 128.73 (CH,2C), 132.56 (CH, 2C), 133.26 (C), 137.91 (C), 138.20 (C), 138.31 (C).

HRMS (FAB) m/z: Calcd for C₄₀H₄₈O₈PS (M+H)⁺, 719.2808; Found 719.2810.

EXAMPLE 9 Phenyl 3,4,6-tri-O-benzyl-2-O-(2,2-dimethyltrimethylenephosphonoyl)-β-D-thioglucopyranoside

Yield: 94%

Properties: amorphous powder

¹H NMR (400 MHz, CDCl₃): 0.90 (s, 3H), 1.24 (s, 3H), 3.53-3.60 (m, 1H),3.62 (t, J=9.2 Hz, 1H), 3.69 (dd, J=11.0, 4.6 Hz, 1H), 3.76 (dd, J=10.8,2.0 Hz, 1H), 3.83 (t, J=8.8 Hz, 1H), 3.86-4.02 (m, 2H), 4.12 (dd,J=10.8, 4.8 Hz, 1H), 4.19 (dd, J=11.2, 4.8 Hz, 1H), 4.40 (dt, J=12.8,9.2 Hz, 1H), 4.51 (d, J=12.0 Hz, 1H), 4.54 (d, J=12.8 Hz, 1H), 4.57 (d,J=12.0 Hz, 1H), 4.75 (d, J=12.8 Hz, 1H), 4.75 (d, J=9.6 Hz, 1H), 4.78(d, J=10.0 Hz, 1H), 4.92 (d, J=10.4 Hz, 1H), 7.14-7.19 (m, 2H),7.22-7.36 (m, 14H), 7.36-7.41 (m, 2H), 7.58-7.63 (m, 2H).

EXAMPLE 10 Phenyl 3,4,6-tri-O-benzyl-2-O-(benzylidenephosphoronoyl)-β-D-thioglucopyranoside

Yield: 84%

Properties: white powder

¹H NMR (400 MHz, CDCl₃): 3.55 (ddd, J=9.6, 4.6, 1.8 Hz, 1H), 3.64 (t,J=9.4 Hz, 1H), 3.70 (dd, J=11.0, 4.6 Hz, 1H), 3.73-3.82 (m, 2H),4.44-4.54 (m, 1H), 4.51 (d, J=12.0 Hz, 1H), 4.54 (d, J=11.6 Hz, 1H),4.57 (d, J=12.0 Hz, 1H), 4.72 (d, J=9.6 Hz, 1H), 4.75 (d, J=10.6 Hz,1H), 4.82 (d, J=10.6 Hz, 1H), 4.92-5.05 (m, 2H), 5.19-5.36 (m, 3H),7.13-7.20 (m, 2H), 7.20-7.37 (m, 18H), 7.38-7.43 (m, 2H), 7.60-7.65 (m,2H).

EXAMPLE 11 Cyclohexyl3,4,6-tri-O-benzyl-2-O-(1,1,2,2-tetramethyldimethylenephosphornoyl)-β-D-glucopyranoside

Tf₂O (33.9 mg, 0.12 mmol) was added at 60° C. to a mixture solution ofthe 2-phosphonoylphenylglucoside compound (63.9 mg, 0.09 mmol) preparedin Example 1, BSP (20.9 mg, 0.10 mmol), DTBMP (39.0 mg, 0.18 mmol) and0.9 ml of dichloromethane containing about 90 mg of molecular sieves 4A.Cyclohexanol (13.0 mg, 0.14 mmol) was added to the solution 30 minuteslater. Et₃N (0.09 ml) was further added to the mixture 30 minutes laterto quench the reaction. The reaction mixture was warmed up to roomtemperature and neutralized with saturated aqueous sodium bicarbonatesolution. The organic layer was separated off, the aqueous layer portionwas subjected to extraction with ethyl acetate three times, and theextraction organic layers were all combined together and washed withsaturated saline solution. The washed layer was thereafter dried overmagnesium sulfate and subsequently filtered, and the filtrate wasdistilled in a vacuum to remove the organic solvent. The desired productwas obtained from the residue by flash chromatography.

Yield: 87%

Properties: amorphous white powder

Isomers ratio α:β=<1:99

¹H NMR (400 MHz, CDCl₃): 1.17-1.30 (m, 2H), 1.37 (s, 3H), 1.38 (s, 3H),1.44 (s, 3H), 1.45 (s, 3H), 1.44-1.58 (m, 4H), 1.72-1.82 (m, 2H),1.86-1.99 (m, 2H), 3.47 (ddd, J=9.7, 5.3, 1.9 Hz 1H), 3.57 (t, J=9.2 hz,1H), 3.60-3.71 (m, 2H), 3.69 (t, J=9.0 Hz, 1H), 3.73 (dd, J=10.8, 2.0Hz, 1H), 4.40 (ddd, J=10.7, 9.1, 7.9 Hz 1H), 4.49 (d, J=8.0 Hz, 1H),4.52 (d, J=11.2 Hz, 1H), 4.55 (d, J=12.0 Hz, 1H), 4.59 (d, J=12.0 Hz,1H), 4.73 (d, J=10.8 Hz, 1H), 4.78 (d, J=10.8 Hz, 1H), 4.94 (d, J=10.4Hz, 1H), 7.12-7.19 (m, 2H), 7.23-7.35 (m, 11H), 7.38-7.43 (m, 2H).

¹³C NMR (100 MHz, CDCl₃): 23.70 (CH₃, J_(CP)=3.1 Hz), 23.76 (CH₃,J_(CP)=3.0 Hz), 23.81 (CH₂), 23.91 (CH₂), 24.09 (CH₃, J_(CP)=2.2 Hz),24.15 (CH₃, J_(CP)=3.1 Hz), 25.64 (CH₂), 31.48 (CH₂), 33.37 (CH₂), 68.96(CH₂), 73.36 (CH₂), 74.89 (CH₂), 75.04 (CH₂), 75.07 (CH), 77.75 (CH),78.03 (CH), 79.55 (CH, J_(CP)=6.8 Hz), 83.56 (CH, J_(CP)=4.6 Hz), 87.88(C, J_(CP)=9.2 Hz, 2C), 99.68 (CH, J_(CP)=3.1 Hz), 127.48 (CH), 127.53(CH), 127.62 (CH, 2C), 127.69 (CH), 127.91 (CH, 2C), 128.20 (CH, 2C),128.28 (CH, 2C), 128.30 (CH, 2C), 128.33 (CH, 2C), 137.99 (C), 138.21(C), 138.24 (C).

In the same manner, Examples 12 to 22 were conducted.

EXAMPLE 12 Methyl 3,4,6-tri-O-benzyl-2-O-(diphenoxyphosphonoyl)-β-D-glucopyranoside

Yield: 88%

Properties: amorphous white powder

Isomers ratio α:β=<1:99

¹H NMR (400 MHz, CDCl₃): 3.35 (s, 3H), 3.50 (ddd, J=9.6, 4.4, 2.0 Hz,1H), 3.65-3.80 (m, 4H), 4.38 (d, J=7.6 Hz, 1H), 4.48-4.57 (m, 3H), 4.61(d, J=12.4 Hz, 1H), 4.75 (d, J=10.8 Hz, 1H), 4.75 (d, J=12.4 Hz, 1H),4.83 (d, J=10.8 Hz, 1H), 7.05-7.35 (m, 15H).

EXAMPLE 13 Cyclohexyl 3,4,6-tri-O-benzyl-2-O-(trimethylenephosphonoyl)-β-D-glucopyranoside

Yield: 84%

Properties: amorphous white powder

Isomers ratio α:β=<1:99

¹H NMR (400 MHz, CDCl₃): 1.12-1.59 (m, 6H), 1.70-1.82 (m, 3H), 1.91-2.04(m, 2H), 2.12-2.26 (m, 1H), 3.51 (ddd, J=9.7, 5.1, 1.9 Hz 1H), 3.58-3.72(m, 3H), 3.73 (dd, J=10.8, 2.0 Hz, 1H), 3.80 (t, J=9.0 Hz, 1H), 4.27(ddd, J=11.8, 9.2, 7.8 Hz, 1H), 4.30-4.46 (m, 4H), 4.54 (d, J=11.2 Hz,1H), 4.54 (d, J=12.4 Hz, 1H), 4.60 (d, J=12.4 Hz, 1H), 4.62 (d, J=7.6Hz, 1H), 4.79 (d, J=10.0 Hz, 2H), 4.96 (d, J=10.4 Hz, 1H), 7.15-7.20 (m,2H), 7.23-7.36 (m, 11H), 7.38-7.43 (m, 2H).

¹³C NMR (100 MHz, CDCl₃): 24.03 (CH₂), 24.13 (CH₂), 25.55 (CH₂), 25.91(CH₂, J_(CP)=6.9 Hz), 31.74 (CH₂), 33.64 (CH₂), 68.18 (CH₂, J_(CP)=6.9Hz), 68.28 (CH₂, J_(CP)=7.7 Hz), 68.79 (CH₂), 73.34 (CH₂), 74.86 (CH₂),74.89 (CH), 74.25 (CH₂), 77.89 (CH), 78.01 (CH), 79.49 (CH, J_(CP)=6.8Hz), 83.50 (CH, J_(CP)=3.0 Hz), 99.28 (CH, J_(CP)=3.1 Hz), 127.52 (CH),127.59 (CH, 3C), 127.75 (CH), 127.85 (CH, 2C), 128.17 (CH, 2C), 128.24(CH, 2C), 128.30 (CH, 2C), 128.36 (CH, 2C), 137.87 (C), 138.12 (C),138.14 (C).

HRMS (FAB) m/z: Calcd for C₃₆H₄₆O₉P (M+H)⁺, 653.2879; Found 653.2886.

EXAMPLE 14 Cyclohexyl 3,4,6-tri-O-benzyl-2-O-(2-methyltrimethylenephosphonoyl)-β-D-glucopyranoside

Yield: 82% (diastereo ratio 80:20)

Properties: amorphous white powder

Isomers ratio α:β=<1:99

EXAMPLE 15 Cyclohexyl3,4,6-tri-O-benzyl-2-O-[(1R,3R)-1,3-dimethyltrimethylenephosphornoyl]-β-D-glucopyranoside

Yield: 65%

Properties: amorphous white powder

Isomers ratio α:β=0:100

¹H NMR (400 MHz, CDCl₃): 1.14-1.34 (m, 3H), 1.34-1.56 (m, 9H), 1.70-2.02(m, 6H), 3.49 (ddd, J=9.9, 5.1, 1.9 Hz 1H), 3.59 (t, J=9.2 Hz, 1H),3.61-3.72 (m, 2H), 3.73 (dd, J=10.8, 2.0 hz, 1H), 3.76 (t, J=8.8 Hz,1H), 4.29 (ddd, J=12.0, 9.2, 8.0 Hz, 1H), 4.52 (d, J=10.8 Hz, 1H), 4.54(d, J=12.0 Hz, 1H), 4.57 (d, J=10.0 Hz, 1H), 4.60 (d, J=12.0 Hz, 1H),4.62-4.73 (m, 1H), 4.73-4.84 (m, 1H), 4.76 (d, J=10.8 Hz, 1H), 4.78 (d,J=11.2 Hz, 1H), 4.95 (d, J=10.4 Hz, 1H), 7.13-7.18 (m, 2H), 7.23-7.35(m, 11H), 7.39-7.44 (m, 2H).

EXAMPLE 16 Cyclohexyl3,4,6-tri-O-benzyl-2-O-[(1S,3S)-1,3-dimethyltrimethylenephosphornoyl]-β-D-glucopyranoside

Yield: 81%

Properties: amorphous white powder

Isomers ratio α:β=<1:99

¹H NMR (400 MHz, CDCl₃): 1.13-1.34 (m, 3H), 1.34-1.58 (m, 9H), 1.72-2.03(m, 6H), 3.49 (ddd, J=9.8, 5.0, 2.0 Hz, 1H), 3.59 (t, J=9.4 Hz, 1H),3.62-3.71 (m, 2H), 3.73 (dd, J=11.2, 2.0 Hz, 1H), 3.73 (t, J=8.8 Hz,1H), 4.29 (ddd, J=11.4, 9.2, 7.8 Hz, 1H), 4.52 (d, J=10.8 Hz, 1H), 4.54(d, J=12.0 Hz, 1H), 4.56 (d, J=7.6 Hz, 1H), 4.59 (d, J=12.0 Hz, 1H),4.62-4.72 (m, 1H), 4.72-4.84 (m, 1H), 4.75 (d, J=10.4 Hz, 1H), 4.79 (d,J=10.8 Hz, 1H), 4.98 (d, J=10.8 Hz, 1H), 7.14-7.20 (m, 2H), 7.22-7.36(m, 11H), 7.39-7.45 (m, 2H).

¹³C NMR (100 MHz, CDCl₃): 21.35 (CH₃, J_(CP)=5.3 Hz), 21.75 (CH₃,J_(CP)=6.8 Hz), 23.92 (CH₂), 24.05 (CH₂), 25.59 (CH₂), 31.68 (CH₂),33.52 (CH₂), 37.83 (CH₂, J_(CP)=6.8 Hz), 68.87 (CH₂), 72.61 (CH,J_(CP)=6.8 Hz), 73.24 (CH, J_(CP)=6.1 Hz), 73.31 (CH₂), 74.86 (CH₂),74.92 (CH), 75.28 (CH₂), 77.77 (CH, 2C), 79.45 (CH, J_(CP)=7.7 Hz),83.80 (CH, J_(CP)=3.8 Hz), 99.45 (CH, J_(CP)=3.8 Hz), 127.46 (CH),127.50 (CH), 127.57 (CH, 2C), 127.69 (CH), 127.85 (CH, 2C), 128.17 (CH,4C), 128.25 (CH, 2C), 128.31 (CH, 2C), 137.91 (C), 138.15 (C), 138.18(C).

EXAMPLE 17 Cyclohexyl 3,4,6-tri-O-benzyl-2-O-(1,1-dimethyltrimethylenephosphonoyl)-β-D-glucopyranoside

Yield: 40% (diastereo ratio 67:33)

Properties: amorphous white powder

Isomers ratio α:β=<1:99

EXAMPLE 18 Cyclohexyl3,4,6-tri-O-benzyl-2-O-(1,1,3,3-tetramethyltrimethylenephosphonoyl)-β-D-glucopyranoside

Yield: 34%

Properties: amorphous white powder

Isomers ratio α:β=<1:99

¹H NMR (400 MHz, CDCl₃): 1.16-2.12 (m, 24H), 3.49 (ddd, J=9.8, 5.2, 1.8Hz, 1H), 3.57 (t, J=7.4 Hz, 1H), 3.58-3.77 (m, 4H), 4.34 (ddd, J=11.8,9.0, 7.8 Hz, 1H), 4.48-4.62 (m, 4H), 4.75 (d, J=10.8 Hz, 1H), 4.78 (d,J=11.2 Hz, 1H), 4.99 (d, J=10.4 Hz, 1H), 7.14-7.20 (m, 2H), 7.22-7.35(m, 11H), 7.40-7.45 (m, 2H).

EXAMPLE 19 Cyclohexyl 3,4,6-tri-O-benzyl-2-O-(2,2-dimethyltrimethylenephosphonoyl)-β-D-glucopyranoside

Yield: 77%

Properties: amorphous white powder

Isomers ratio α:β=0:100

¹H NMR (400 MHz, CDCl₃): 0.87 (s, 3H), 1.12-1.58 (m, 8H), 1.70-1.82 (m,3H), 1.90-2.04 (m, 2H), 3.50 (ddd, J=9.6, 5.0, 1.8 Hz, 1H), 3.61 (t,J=9.4 Hz, 1H), 3.62-3.71 (m, 2H), 3.73 (dd, J=11.0, 1.8 Hz, 1H), 3.80(t, J=9.0 Hz, 1H), 3.83-4.16 (m, 4H), 4.22-4.32 (m, 1H), 4.51-4.64 (m,4H), 4.78 (d, J=10.4 Hz, 1H), 4.79 (d, J=11.2 Hz, 1H), 4.95 (d, J=10.4Hz, 1H), 7.15-7.21 (m, 2H), 7.24-7.36 (m, 11H), 7.37-7.44 (m, 2H).

EXAMPLE 20 Cyclohexyl 3,4,6-tri-O-benzyl-2-O-(benzylidenephosphoronoyl)-β-D-glucopyranoside

Yield: 87%

Properties: amorphous white powder

Isomers ratio α:β=<1:99

¹H NMR (400 MHz, CDCl₃): 1.17-1.68 (m, 5H), 1.71-1.84 (m, 3H), 1.90-2.02(m, 2H), 3.49 (ddd, J=9.7, 5.1, 1.9 Hz 1H), 3.61 (t, J=9.2 Hz, 1H), 3.65(dd, J=10.8, 5.2 Hz, 1H), 3.64-3.74 (m, 1H), 3.73 (dd, J=11.0, 1.8 Hz,1H), 3.75 (t, J=9.0 Hz, 1H), 4.39 (dt, J=9.6, 7.9 Hz 1H), 4.50-4.62 (m,4H), 4.78 (d, J=10.4 Hz, 2H), 4.97 (d, J=10.8 Hz, 1H), 5.04-5.32 (m,4H), 7.14-7.68 (m, 19H).

EXAMPLE 212,3,6-tir-O-benzyl-4-O-[3′,4′,6′-tri-O-benzyl-2′-O-(1,1,2,2-tetramethyldimethylenephosphonoyl)-β-D-glucopyranosyl]-β-D-thioglucopyranoside

Yield: 56%

Properties: amorphous white powder

Isomers ratio α:β=9:91

¹H NMR (400 MHz, CDCl₃): 1.30 (s, 3H), 1.33 (s, 3H), 1.38 (s, 3H), 1.46(s, 3H), 3.34 (br dd, J=9.6, 2.8 Hz, 1H), 3.42 (t, J=9.4 Hz, 1H),3.47-3.56 (m, 3H), 3.60-3.80 (m, 4H), 3.95 (dd, J=11.2, 3.2 Hz, 1H),4.08 (t, J=9.4 Hz, 1H), 4.33 (d, J=12.0 Hz, 1H), 4.37 (d, J=12.0 Hz,1H), 4.37-4.49 (m, 1H), 4.50 (d, J=9.6 Hz, 1H), 4.50 (d, J=12.0 Hz, 1H),4.58 (d, J=8.0 Hz, 1H), 4.63 (d, J=1.0 Hz, 1H), 4.68-4.76 (m, 6H), 4.87(d, J=10.8 Hz, 1H), 5.13 (d, J=11.2 Hz, 1H), 7.10-7.16 (m, 4H),7.18-7.35 (m, 27H), 7.36-7.40 (m, 2H), 7.54-7.60 (m, 2H).

¹³C NMR (100 MHz, CDCl₃): 23.69 (CH₃, J_(CP)=6.9 Hz), 23.87 (CH₃,J_(CP)=6.9 Hz), 24.11 (CH₃, J_(CP)=3.0 Hz), 24.43 (CH₃, J_(CP)=3.8 Hz),68.27 (CH₂), 68.77 (CH₂), 73.27 (CH₂), 73.47 (CH₂), 74.74 (CH₂), 75.13(CH₂), 75.21 (CH₂), 75.30 (CH), 75.68 (CH₂), 76.04 (CH), 77.88 (CH),78.83 (CH), 79.67 (CH, J_(CP)=6.9 Hz), 79.79 (CH), 83.24 (CH, J_(CP)=3.8Hz), 84.85 (CH), 87.09 (CH), 87.92 (C), 88.33 (C), 99.99 (CH, J_(CP)=3.9Hz), 126.94 (CH), 127.21 (CH), 127.28 (CH), 127.34 (CH, 2C), 127.39(CH), 127.42 (CH), 127.52 (CH), 127.55 (CH, 3C), 127.60 (CH, 2C), 127.85(CH, 2C), 127.88 (CH, 6H), 128.06 (CH, 2C), 128.09 (CH, 4C), 128.18 (CH,2C), 128.33 (CH, 2C), 128.67 (CH, 2C), 132.10 (CH, 2C), 133.34 (C),137.88 (C), 137.97 (C), 138.05 (C), 138.13 (C), 138.14 (C), 138.99 (C).

HRMS (FAB) m/z: Calcd for C₆₆H₇₄O₁₃PS (M+H)⁺, 1137.4588; Found1137.4596.

EXAMPLE 226-O-[6′-O-tert-butyldimethylsilyl-2′-O-(2,2-dimethyltrimethylenephosphonoyl)-3′,4′-O-propyridene-β-D-glucopyranosyl]-2-O-(2,2-dimethyltrimethylenephosphonoyl)-3,4-O-propyridene-β-D-thioglucopyranoside

Yield: 67% (α:β=9:91)

Properties: amorphous white powder

Isomers ratio α:β=9:91

¹H NMR (400 MHz, CDCl₃): 0.07 (s, 6H), 0.77 (s, 3H), 0.89 (s, 3H), 0.89(s, 9H), 1.19 (s, 3H), 1.25 (s, 3H), 1.34 (s, 3H), 1.35 (s, 3H), 1.51(s, 3H), 1.56 (s, 3H), 3.70-4.28 (m, 17H), 4.32-4.49 (m, 3H), 4.61 (d,J=8.0 Hz, 1H), 4.86 (d, J=8.8 Hz, 1H), 7.22-7.36 (m, 3H), 7.52-7.58 (m,2H).

EXAMPLE 23 Deprotection Deprotection of2,3,6-tir-O-benzyl-4-O-[2′-O-acetyl-3′,4′,6′-tri-O-benzyl-β-D-glucopyranosyl]-β-D-thioglucopyranoside

A solution of sodium (7.6 mg, 0.331 mmol) in 1 4-dioxane (0.50 ml) wasadded at room temperature to the 2-phosphonoyl-1,2-glycoside compound(20.5 mg, 0.018 mmol) prepared in Example 21, and the reaction mixturewas neutralized with saturated aqueous solution of ammonium chloride 2hours later. The organic layer was separated off, and the aqueous layerwas subjected to extraction with ethyl acetate three times. The extractsand the organic layer were combined together, washed with saturatedaqueous saline solution, dried over magnesium sulfate and concentratedin a vacuum to obtain a residue (20.5 mg). The residue was an alcoholcompound resulting from the removal of the phosphonoyl group at the2-position.

The residue (14.9 mg) was dissolved in methylene chloride (0.5 ml), andacetic anhydride (8.0 mg, 0.078 mmol), triethylamine (8.0 mg, 0.079mmol) and DMAP (1.0 mg, 0.0082 mmol) were added to the solution at roomtemperature. The reaction mixture was neutralized with saturated aqueoussolution of sodium hydrogencarbonate 2 hours later. The organic layerwas separated off, and the aqueous layer was subjected to extractionwith ethyl acetate three times. The extracts and the organic layer werecombined together, washed with saturated aqueous saline solution, driedover magnesium sulfate and concentrated in a vacuum. The resultingresidue was purified by flash chromatography (silica gel 1.0 g; elutionwith 30% ethyl acetate in hexane) to obtain a 2-acetoxyglycosidecompound.

Yield: 90%

Properties: amorphous white powder

¹H NMR (400 MHz, CDCl₃): 1.82 (s, 3H), 3.20-3.27 (m, 1H), 3.30 (dt,J=9.9, 2.7 Hz, 1H), 3.35 (t, J=9.2 Hz, 1H), 3.39-3.48 (m, 2H), 3.32-3.72(m, 5H), 3.87 (t, J=9.6 Hz, 1H), 4.22-4.32 (m, 2H), 4.44 (d, J=12.0 Hz,2H), 4.47-4.73 (m, 9H), 4.88 (dd, J=9.0, 8.2 Hz, 1H), 5.03 (d, J=11.6Hz, 1H), 7.04-7.28 (m, 33H), 7.43-7.49 (m, 2H).

¹³C NMR (100 MHz, CDCl₃): 21.08 (CH₃), 68.07 (CH₂), 68.60 (CH₂), 73.23(CH₂), 73.52 (CH₂), 73.65 (CH), 74.87 (CH₂), 75.07 (CH₂), 75.16 (CH),75.30 (CH₂), 75.39 (CH₂), 76.62 (CH), 77.98 (CH), 78.98 (CH), 80.23(CH), 83.01 (CH), 84.75 (CH), 87.40 (CH), 100.28 (CH), 127.00 (CH),127.30 (CH, 2C), 127.39 (CH, 2C), 127.44 (CH, 2C), 127.57 (CH, 4C),127.60 (CH), 127.65 (CH, 2C), 127.68 (CH), 127.79 (CH, 2C), 127.96 (CH,2C), 128.04 (CH, 2C), 128.13 (CH, 4C), 128.26 (CH, 2C), 128.30 (CH, 4C),128.72 (CH, 2C), 131.85 (CH, 2C), 133.52 (C), 137.73 (C), 137.87 (C),137.90 (C), 137.96 (C), 138.06 (C), 138.94 (C), 169.09 (C═O).

INDUSTRIAL APPLICABILITY

According to the present invention, a specified phosphoric acid ester(phosphonoyl group) is used as a saccharide donor for glycosilation as aprotective group for the hydroxyl group at the second position of afuranose compound or pyranose compound to thereby form a glycosidelinkage of 1,2-trans form selectively, inhibit the formation of aby-product corresponding to an o-ester and make it possible to lengthenthe saccharide chain as desired.

1. A process for preparing a glycoside compound comprising a glycosidicbond that selectively forms a trans configuration relative to the C-2hydroxyl group, the process comprising reacting a furanose compound or apyranose compound with an alcohol compound, wherein the hydroxyl at theC-2 position of the furanose compound or the pyranose compound isprotected with a group A,

wherein R² and R³ are connected via an alkylene group having 2 to 4carbon atoms, further wherein the alkylene group is optionallysubstituted with an alkyl group having 1 to 4 carbon atoms, oroptionally comprises an intervening phenylene, and m and n are each aninteger of 0 or 1; and the furanose compound or the pyranose compoundoptionally comprises a substituent.
 2. The process of claim 1, whereinthe furanose compound is arabofuranose, erythrofuranose, glucofuranose,ribofuranose, threofuranose or xylofuranose; the pyranose compound isarabopyranose, altropyranose, glucopyranose, galactopyranose,glopyranose, mannopyranose, ribopyranose, xylopyranose orglucopyranuronic acid; and the alcohol compound is an aliphatic alcoholcomprising 1 to 4 carbon atoms, alicyclic alcohol comprising 5 to 8carbon atoms, aromatic alcohol, furanose, pyranose, aminopyranose,anhydrosugar, polysaccharide, N-acetylpyranose or glycerol.
 3. A processfor preparing a 2-phosphonoyl-1,2-transglycoside compound of formula (3)comprising reacting an alcohol compound of formula (2) with a2-phosphonoylpyranose compound of formula (1), formula (1) comprising:Q¹-Z  (1) wherein Q¹=

Z is a group —S—R¹, a group —SO—R¹, a group —Se—R¹, a group—O—C(═NH)CX₃, a halogen atom, an alkoxyl, an alkenyloxy, a group—P(OR¹)₃ or a group —PO(OR¹)₃, R¹ is an alkyl comprising 1 to 20 carbonatoms, an aryl optionally substituted or a heteroaromatic group, X is ahalogen atom, R⁴, R⁵ and R⁶ are the same or different and are each aprotective group for the saccharide hydroxyl group, E is methylene or acarbonyl, and A is

wherein R² and R³ are connected via an alkylene group having 2 to 4carbon atoms, further wherein the alkylene group is optionallysubstituted with an alkyl group having 1 to 4 carbon atoms, oroptionally comprises an intervening phenylene, and m and n are each aninteger of 0 or 1; formula (2) comprising:Q²-OH  (2) wherein Q² is an alkyl having 1 to 4 carbon atoms, acycloalkyl comprising 5 to 8 carbon atoms, optionally substituted, orone of the following groups

wherein L¹ is a group —OA¹, —OG or —N(J¹)(J²), A¹ is a group shownbelow, G is a protective group for the saccharide hydroxyl, and J¹ andJ² are each a hydrogen atom or a protective group for amino

R^(2′) and R^(3′) are combined with each other to form an alkylenehaving 2 or 4 carbon atoms, further, wherein the alkylene is optionallysubstituted with alkyl having 1 to 4 carbon atoms, or optionallycomprises an intervening phenylene, m′ and n′ are each an integer of 0or 1, Z¹ is a group —S—R^(1′), a group —SO—R^(1′), a group —Se—R^(1′), agroup —O—C(═NH)CX′₃, a halogen atom, an alkoxyl, an alkenyloxy, a group—P(OR¹')₃, a group —PO(OR^(1′))₃ or —OG¹, R^(1′) is an alkyl comprising1 to 20 carbon atoms, an aryl optionally substituted or a heteroaromaticgroup, X′ is a halogen atom, G¹ is a protective group for the saccharidehydroxyl, R⁷, R⁸ and R⁹ are the same or different and are each aprotective group for the saccharide hydroxyl group, and E¹ is methyleneor a carbonyl; and formula (3) comprising:Q^(1a)-O-Q²  (3) wherein Q^(1a)=

and Q², A, R⁴, R⁵ and R⁶ are as defined above.
 4. A process forpreparing a 2-phosphonoyl-1,2-transglycoside compound of formula (3a)comprising reacting an alcohol compound of formula (2a) with a2-phosphonoylpyranose compound of formula (1), formula (1) comprising:Q¹-Z  (1) wherein Q¹=

Z is a group —S—R¹, a group —SO-R¹, a group —Se—R¹, a group—O-C(=NH)CX₃, a halogen atom, an alkoxyl, an alkenyloxy, a group—P(OR¹)₃ or a group —PO(OR¹)₃, R¹ is an alkyl comprising 1 to 20 carbonatoms, an aryl optionally substituted or a heteroaromatic group, X is ahalogen atom, R⁴, R⁵ and R⁶ are the same or different and are each aprotective group for the saccharide hydroxyl group, E is methylene or acarbonyl, and A is

wherein R² and R³ are connected via an alkylene group having 2 to 4carbon atoms, further wherein the alkylene group is optionallysubstituted with an alkyl group having 1 to 4 carbon atoms, oroptionally comprises an intervening phenylene, and m and n are each aninteger of 0 or 1; formula (2a) comprising:Q^(2a)-OH  (2a) wherein Q^(2a) is one of the groups given below,

A¹ is

R^(2′) and R^(3′) are combined with each other to form an alkylenehaving 2 or 4 carbon atoms, further, wherein the alkylene is optionallysubstituted with alkyl having 1 to 4 carbon atoms, or optionallycomprises an intervening phenylene, m′ and n′ are each an integer of 0or 1; R⁷, R⁸, R⁹ are the same or different and are each a protectivegroup for the saccharide hydroxyl group, and E¹ is methylene orcarbonyl, Z² is a group —S—R^(1′), a group —SO—R^(1′), a group—Se—R^(1′), a group —O—C(═NH)CX'₃, a halogen atom, an alkoxyl, analkenyloxy, a group —P(OR^(1′))₃ or a group —PO(OR^(1′))₃, R^(1′) is analkyl comprising 1 to 20 carbon atoms, an aryl optionally substituted,or a heteroaromatic group, and X is a halogen atom; and formula (3a)comprising:Q^(1a)-O-Q^(2a)  (3a) wherein Q^(1a) =

R⁴, R⁵ and R⁶ are the same or different and are each a protective groupfor the saccharide hydroxyl group, E is methylene or a carbonyl, and Ais

wherein R² and R³ are connected via an alkylene group having 2 to 4carbon atoms, further wherein the alkylene group is optionallysubstituted with an alkyl group having 1 to 4 carbon atoms, oroptionally comprises an intervening phenylene, and m and n are each aninteger of 0 or 1; and Q^(2a) is as defined above.
 5. A process forpreparing a 2-phosphonoyl-1,2-transglycoside compound comprisingoptionally repeating the step of reacting an alcohol compound of formula(2a) with a 2-phosphonoyl-1,2-transglycoside compound of formula (3a) atleast once, formula 2(a) comprising:Q^(2a)-OH  (2a) wherein Q^(2a) is one of the groups given below,

A¹ is

R^(2′) and R^(3′) are combined with each other to form an alkylenehaving 2 or 4 carbon atoms, wherein the alkylene is optionallysubstituted with alkyl having 1 to 4 carbon atoms, or optionallycomprises an intervening phenylene, m′ and n′ are each an integer of 0or 1; R⁷, R⁸, R⁹ are the same or different and are each a protectivegroup for the saccharide hydroxyl group, and E¹ is methylene orcarbonyl, Z² is a group —S—R^(1′), a group —SO—R^(1′), a group—Se—R^(1′), a group —O—C(═NH)CX′₃, a halogen atom, an alkoxyl, analkenyloxy, a group —P(OR^(1′))₃ or a group —PO(OR^(1′))₃; R^(E) is analkyl comprising 1 to 20 carbon atoms, an aryl optionally substituted,or a heteroaromatic group, and X′ is a halogen atom; and formula (3a)comprising:Q^(1a)-O-Q^(2a)  (3a) wherein Q^(1a)=

R⁴, R⁵ and R⁶ are the same or different and are each a protective groupfor the saccharide hydroxyl group, E is methylene or a carbonyl, and Ais

wherein R² and R³ are connected via an alkylene group having 2 to 4carbon atoms, further wherein the alkylene group is optionallysubstituted with an alkyl group having 1 to 4 carbon atoms, oroptionally comprises an intervening phenylene, and m and n are each aninteger of 0 or 1; and Q^(2a) is as defined above.
 6. A process forpreparing a 1,2-transglycoside compound of the formula (4) comprisingreacting a base with a 2-phosphonoyl-1,2-transglycoside compound offormula (3), formula (3) comprising:Q^(1a)-O-Q²  (3) wherein Q^(1a)=

R⁴, R⁵, R⁶ and E are as defined below, and A is

wherein R² and R³ are connected via an alkylene group having 2 to 4carbon atoms, further wherein the alkylene group is optionallysubstituted with an alkyl group having 1 to 4 carbon atoms, oroptionally comprises an intervening phenylene, and m and n are each aninteger of 0 or 1; wherein Q² is an alkyl having 1 to 4 carbon atoms, acycloalkyl comprising 5 to 8 carbon atoms, optionally substituted, orone of the following groups

wherein L¹ is a group —OA¹, —OG or —N(J¹)(J²), A¹ is a group shownbelow, G is a protective group for the saccharide hydroxyl, and J¹ andJ² are each a hydrogen atom or a protective group for amino

R^(2′) and R^(3′) are combined with each other to form an alkylenehaving 2 or 4 carbon atoms, further, wherein the alkylene is optionallysubstituted with alkyl having 1 to 4 carbon atoms, or optionallycomprises an intervening phenylene, m′ and n′ are each an integer of 0or 1, Z¹, X′, R⁷, R⁸, R⁹, and E¹ are as defined below; formula (4)comprising:Q³-O-Q⁴  (4) wherein Q³=

R⁴, R⁵, R⁶ are the same or different and are each a protective group forthe saccharide hydroxyl group, and E is methylene or a carbonyl, and Q⁴is an alkyl comprising 1 to 4 carbon atoms, a cycloalkyl comprising 5 to8 carbon atoms, optionally substituted, or one of the groups given below

wherein L² is the group —OH, —OG or —N(J¹)(J²), Z¹ is a group —S—R^(1′),a group —SO—R^(1′), a group —Se—R^(1′), a group —O—C(═NH)CX'₃, a halogenatom, an alkoxyl, an alkenyloxy, a group —P(OR^(1′))₃, a group—PO(OR^(1′))₃ or —OG¹, R^(1′) is an alkyl comprising 1 to 20 carbonatoms, an aryl optionally substituted, or a heteroaromatic group, X′ isa halogen atom, G¹ is a protective group for the saccharide hydroxyl,R⁷, R⁸ and R⁹ are the same or different and are each a protective groupfor the saccharide hydroxyl group, E¹ is methylene or a carbonyl, G is aprotective group for the saccharide hydroxyl, and J¹ and J² are each ahydrogen atom or a protective group for amino.